Schering Corporation

Ribapharm Inc.

Nanhua Hugh Yao

Patricia C Weber

Vincent Stewart Madison

Viyyoor Moopil Girijavallabhan

Ashit K Ganguly

Ashok Arasappan

Srikanth Venkatraman

Paul Reichert

Kevin X Chen

Bruce A Malcolm

Andrew Joseph Prongay

S Shane Taremi

F George Njoroge

Anil K Saksena

Zhi Hong

Tin-Yau Chan

Haoyun An

Edwin Jao

Bancha Vibulbhan

Shahriar Shane Taremi

Winifred W Prosise

Tejal Parekh

George F Njoroge

Yili Ding

Brian Alexander Mc Kittrick

Jennifer Joanne Gesell

Daniel F Wyss

Dingjiang Liu

Todd Appleby

Shahul Nilar

Haining Gu

This invention provides fragments of HCV NS3 helicase, and crystalline compositions thereof, based on subdomains of HCV helicase protein. The protein fragments are stable, soluble, and structurally sound. They can be expressed at high levels in conventional expressions systems, such as, to permit efficient, large-scale production for NMR-based screening applications and production of [H,C,N]- and [C,N]-labeled polypeptides for structural NMR studies. Helicase fragments of the present invention are useful in the most advanced NMR techniques available, e.g., NMR-based drug discovery techniques such as SAR-by-NMR, in biological assays to discover inhibitors of HCV NS3 helicase, and to evaluate the mechanism of action and substrates for HCV NS3 helicase. Crystals of the present invention are useful for structure-based drug design studies using x-ray crystallographic techniques.

Hepatitis C virus NS3 helicase subdomain I

The present invention discloses novel macrocyclic compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such macrocycles as well as methods of using them to treat disorders associated with the HCV protease.

Macrocyclic NS-3 serine protease inhibitors of hepatitis C virus comprising alkyl and aryl alanine P2 moieties

A polymerase inhibitor has first moiety coupled to a second moiety via an optional linker in which the first moiety binds to an initiation nucleotide binding site of a polymerase and forms at least two hydrogen bonds with an RNA template strand that is associated with the polymerase, and in which the second moiety comprised a compound that binds to a site proximal to the nucleotide binding site of the polymerase and thereby increases the affinity of the polymerase inhibitor to the polymerase.

Inhibitors for de novo-RNA polymerases and methods of identifying targets for same

Macrocyclic NS3-serine protease inhibitors of hepatitis C virus comprising N-cyclic P2 moieties

Covalent HCV NS4A-NS3 complexes comprising the central hydrophobic domain of native HCV NS4A peptide, a linker, and the HCV NS3 serine protease domain, wherein the hydrophobic domain of native HCV NS4A peptide is tethered by the linker to the amino terminus of the HCV NS3 protease domain.

Single-chain recombinant complexes of hepatitis C virus NS3 protease and NS4A cofactor peptide

The invention relates to the purification and crystallization of hepatitis C virus (HCV) NS3/NS4A polypeptide complex. Also, crystallization conditions for NS3/NS4A are provided. Further, the atomic coordinates for the NS3/NS4A protein are disclosed. Examples of its use for the determination of the three-dimensional atomic structures of HCV NS3/NS4A with substrate(s) or substrate analog(s) or inhibitor complexes are also provided.

Compositions of hepatitis C virus NS3/NS4A complex and methods for crystallizing same

Growing community of inventors

Edison, NJ, United States of America

Nanhua Hugh Yao